Characteristic distribution patterns of tenascin in laryngeal and hypopharyngeal cancers

OBJECTIVES: Progression of malignant neoplasias is accompanied by alteration of the extracellular matrix (ECM) composition. Tenascin is known as a member of the adhesion-modulating family of ECM macromolecules; thus its expression and distribution may have significant influence on tumor cell proliferation and invasiveness. STUDY DESIGN: The present study was carried out to determine the distribution pattern of tenascin in laryngeal and hypopharyngeal cancer samples. METHODS: In double and triple immunofluorescent staining reactions the detection of tenascin was combined with labelings for cytokeratin (marker protein of epithelial cells), for CD-34 (endothelial cell surface glycoprotein), and for a reaction with Ki-67 monoclonal antibody (nuclear antigen in proliferating cells). RESULTS: In laryngeal cancers, in early stages of tumor growth a markedly enhanced production of tenascin at the tumor host interphase was observed. In the later stages of tumor progression, a high number of blood vessels located in the tumorous tissues were also strongly labeled for tenascin. Around these vessels a significant number of proliferating tumor cells could be detected. In contrast, in hypopharyngeal cancers this vasculature-associated staining pattern could be observed from the very early stage of tumor development. In laryngeal and in hypopharyngeal cancers, tenascin upregulation strongly correlated with metastasis formation, early tumor recurrence, and lethal outcome of the disease. CONCLUSIONS: Clinical and immunohistologic data indicate that the accumulation of tenascin in the tumor blood vessels is an unfavorable prognostic indicator in laryngeal and hypopharyngeal cancers.     

Characterization of c4d immunostaining utilizing paraffin-embedded tissue of nonpresensitized pediatric heart transplant patients.

Immunoperoxidase techniques for demonstration of complement split product C4d on paraffin-embedded endomyocardial biopsy samples have been used for the evaluation of humoral rejection mainly in adult heart transplantation. Interpretation of suspected humoral rejection in children requires knowledge of the pattern and frequency of C4d deposition in nonpresensitized pediatric heart transplantation patients. Paraffin-embedded endomyocardial biopsy samples of 65 patients with no rejection, acute cellular rejection (ACR), or early ischemic/reperfusion injury were studied. Six biopsies within each grade of ACR both early (<6 months) and late (>6 months) after heart transplantation were reviewed, as were 5 biopsies of ischemic/reperfusion injury. None of the subjects was sensitized prior to transplant. All slides were blindly evaluated for histologic features traditionally associated with humoral rejection. C4d staining was quantified by counting the number of positive capillaries in 10 random high-power fields (hpf). C4d positivity (C4d+) was defined as >10 capillaries/10 hpf. C4d+ was observed in 6 (9%) endomyocardial biopsy samples; 2 in the early and 4 in the late ACR groups. Four had ACR grades 1A/B, and 2 had grade 3B/4. Thirteen (20%) endomyocardial biopsy samples had histologic features suggestive of humoral rejection. Of these, only 2 were C4d+ and both had ACR grade 3B/4. No C4d+ staining was found in the ischemic/reperfusion injury group. C4d immunostaining was negative in endomyocardial biopsy samples of the majority of our patients (91%). Endomyocardial biopsy samples with C4d+ did not show consistent ACR grade or time specificity. Contrary to previously reported data, none of the ischemic/reperfusion injury endomyocardial biopsy samples was C4d+, and histologic features alone were poor predictors of C4d+.     

Molecular mechanisms of pulmonary vascular development.

In this era of rapidly advancing vascular biology research, a vast array of growth factors and signaling molecules have been recognized as key players in the mechanisms that control lung vascular development. In the lung, vascular development is a complex, multistep process that includes specialization of primitive cells to vascular progenitors; formation of primitive vascular networks; remodeling with local regression and branching; specialization toward arteries, veins, and lymphatics; stabilization of vessels by matrix production and recruitment of supporting cells; and maintenance of the vascular structure. This complex, highly organized process requires exquisite orchestration of the regulatory activity of multiple molecules in a specific temporospatial order. Most of these molecules are members of 3 major growth factor families that have been recently identified. They are the vascular endothelial growth factor, angiopoietin, and ephrin families. Understanding the functional reach of several members of these growth factor families is integral to an appreciation of the etiology and pathogenesis of developmental lung vascular disorders affecting newborns.This review summarizes recent advances in the molecular bases of lung vascular development and some of the pulmonary diseases resulting from aberrant vascular growth, including bronchopulmonary dysplasia, alveolar capillary dysplasia, congenital cystic pulmonary disorders, congenital pulmonary hemangiomatosis, and lung hypoplasia.     

Thrombotic complications due to oral contraceptives]

Cases reported here as well as the literary date tell attention to the vascular complications following contraceptive therapy. Shift of clotting-fibrinolysis system towards hypercoagulobolity is remarkable because of its role as a risk factor. If contraceptive therapy is accompanied by a condition or a disease altering clotting factors, vessel walls or circulation so that it presents an enhanced thrombosis capacity the risk may increase. In such cases indication of oral contraceptive therapy should be considered cautiously and the patients should be controlled with more intention.     

Quantitative serum levels of pregnancy associated alpha2-globulin in patients with benign and malignant tumours.

Pregnancy associated alpha2-globulin estimations were made in the serum of 100 tumour-cases. This characteristically pregnancy protein could be found in 63 p.c. of the tumour cases. The number of positive sera was higher, than in normal controls. The serum level of pregnancy associated alpha 2-globulin was between 1 and 10 mg p.c. in 34 cases, between 11 and 20 mg p.c. in 19 cases and value above 20 mg p.c. could only be found in 10 patients. This alpha2-globulin positivity could be seen more frequently in female than in male patients. Role and significance of alpha2-globulin is discussed.     

Serum level of pregnancy associated alpha2-globulin in patients with spontaneous abortions.

Pregnancy associated alpha2-globulin serum levels have been measured in abortion-cases. In cases of incomplete abortion with placental destruction and missed abortion this alpha2-globulin level significantly decreased, but no changes could be found when the placenta remained intact. The prognostic value of this pregnancy protein is discussed.     

The role of poly(ADP-ribose) polymerase activation in the development of myocardial and endothelial dysfunction in diabetes.

Patients with diabetes exhibit a high incidence of diabetic cardiomyopathy and vascular complications, which underlie the development of retinopathy, nephropathy, and neuropathy and increase the risk of hypertension, stroke, and myocardial infarction. There is emerging evidence that the activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) importantly contributes to the development of endothelial dysfunction in a streptozotocin-induced model of diabetes. We investigated the role of PARP activation in the pathogenesis of cardiac dysfunction in streptozotocin-induced and genetic (nonobese diabetic) models of diabetes in rats and mice. Development of diabetes was accompanied by hyperglycemia, cardiac PARP activation, a selective loss of endothelium-dependent vasodilation in the thoracic aorta, and an early diastolic dysfunction of the heart. Treatment with a novel potent phenanthridinone-based PARP inhibitor, PJ34, starting 1 week after the onset of diabetes, restored normal vascular responsiveness and significantly improved cardiac dysfunction, despite the persistence of severe hyperglycemia. The beneficial effect of PARP inhibition persisted even after several weeks of discontinuation of the treatment. Thus, PARP activation plays a central role in the pathogenesis of diabetic cardiovascular (cardiac as well as endothelial) dysfunction. PARP inhibitors may exert beneficial effects against the development of cardiovascular complications in diabetes.